Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.2.3 (glutathione synthetase)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conversion of gamma-glutamylcysteinylethyl ester (gamma-GCE) to glutathione in a reduced form (GSH) was examined using isolated rat hepatocytes pretreated with diethylmaleate, a GSH-depletor. Incubation of hepatocytes with 0.1 and 5.0 mM gamma-GCE (gamma-GCE-hepatocytes) over a 30-min period resulted in time-dependent increases in intracellular GSH and nonprotein-SH (NP-SH) concentrations. Hepatocytes incubated with 5.0 mM but not 0.1 mM GSH over a period of 30 min showed a time-dependent increase in intracellular GSH concentration. In the gamma-GCE-hepatocytes pretreated with bis-(p-nitrophenyl)phosphate (BNPP), a non-specific esterase inhibitor, an enhancement of intracellular GSH concentration was markedly reduced. gamma-GCE concentration in the gamma-GCE-hepatocytes with BNPP pretreatment was significantly higher than that in the cells without BNPP pretreatment, although there was no difference in the total amount of intracellular NP-SH, i.e., gamma-GCE, GSH, gamma-glutamylcysteine, cysteine ethyl ester, and cysteine between both gamma-GCE-hepatocytes. The present results indicate that gamma-GCE is transported into liver cells more easily than GSH itself, resulting in its conversion to GSH via esterase and glutathione synthetase within the cells.
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PMID:Conversion of gamma-glutamylcysteinylethyl ester to glutathione in rat hepatocytes. 878 49

Zygotes were collected from transgenic mice overexpressing glutathione synthetase to test the hypothesis that such zygotes are more capable of developing in suboptimal culture media than zygotes from non-transgenic (control) mice. The effects of injection of donor mice with gamma-glutamylcysteinyl ethyl ester (gamma-GCE) on embryonic development were also investigated. In addition, the effects of genetic background (i.e., transgenic vs. non-transgenic) and injection with gamma-GCE on developmental capacity in kSOM were studied after exposure of zygotes to diamide (0.01 mM, for 30 min). When cultured in modified Medium 16 significantly more pronuclear ova from transgenic females reached the morula (M) and early blastocyst (EB) stages than embryos derived from control mice. Genetic background significantly affected the proportions of embryos reaching 4- to 16-cell, M and EB stages during culture in modified Whitten's medium (WM); more zygotes collected from transgenic than from control mice developed. The injection of experimental mice with gamma-GCE significantly increased proportions of zygotes developing to M and EB stages in WM. Following exposure to diamide and subsequent culture in kSOM significantly more zygotes collected from transgenic mice reached the 4- to 16-cell stages than those from control females; a significant positive effect on developmental capacity was also seen after injection of donor mice with gamma-GCE. When cultured in suboptimal conditions, zygotes derived from transgenic mice overexpressing glutathione synthetase were more capable of developing than zygotes of non-transgenic control females. Zygotes from the transgenic mice also exhibited greater capacity to withstand toxic exposure to diamide. Present data suggest that commonly known strain differences in preimplantational development in vitro may reflect differences in the synthesis and/or metabolism of glutathione. J. Exp. Zool. 286:173-180, 2000.
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PMID:Developmental patterns of zygotes from transgenic female mice with elevated tissue glutathione. 1061 59

Previous studies demonstrated that elevation of hepatic glutathione (GSH) concentrations protect against acetaminophen (APAP) hepatotoxicity in mice. Employing transgenic mice overexpressing glutathione synthetase, this study was conducted to determine if sustained elevation of hepatic GSH concentrations could ameliorate or prevent APAP toxicity. International Cancer Research transgenic mouse males and matched (ie same strain, sex, and age) control nontransgenic mice were pretreated ip with GSH synthetase substrate gamma-glutamylcysteinyl ethyl ester (gamma-GCE) or with saline. After a 16-h fast, mice received a single dose of 500 mg APAP/kg bw in saline ip and were sacrificed 4 h later. Other mice similarly pretreated were killed without APAP challenge. The elevated GSH concentrations in transgenic mice livers did not lessen APAP hepatotoxicity. Instead higher degrees of hepatotoxicity and nephrotoxicity were observed in transgenic mice than in controls as indicated by higher serum alanine aminotransferase activity and more severe histopathological lesions in transgenic mice livers and kidneys. Pretreatment with gamma-GCE did not affect either initial or post-APAP treatment tissue GSH concentrations or observed degrees of toxicity. Detection of a higher level of serum APAP in transgenic mice and the histopathological lesions found in transgenic mice kidneys together with no observable nephrotoxicity in control mice indicated early kidney damage in transgenic mice. Our findings suggest that high levels of GSH-APAP conjugates resulting from increased GSH concentrations in the livers of transgenic mice caused rapid kidney damage. Compromised excretory ability may have caused retention of APAP, which, in effect, elicited higher hepatotoxicity than that observed in nontransgenic mice.
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PMID:Acute acetaminophen toxicity in transgenic mice with elevated hepatic glutathione. 1083 17